Apparatuses for the detection of fluorescing areas are known, for example, in the form of a fluorescence microscope or in the form of a fluorescence endoscope. As indicated further below, both exploit the fact that a fluorescing substance builds up more in certain areas of a specimen than in other areas. As a result of irradiation with suitable excitation light, the areas with a greater buildup begin to shine; they fluoresce, or actively emit light at the emission wavelength. Given specific preconditions (as indicated below), this light can be perceived.
Application of the effect with reference to a surgical fluorescence stereomicroscope for the medical sector will be explained below. The explanations are, however, of course not limited to utilization in the medical sector or limited to the field of medical surgical microscopes or to exclusively surgical microscopes, as already indicated above.
Surgical fluorescence microscopes have already been used for some time, for example, in the context of resection of tumors. For this, a photosensitizer or photodynamic medication, for example aminolevulinic acid (ALA) or meso-tetrahydroxyphenyl chlorine (mTHPC), is administered to the patient. This photosensitizer builds up in tumor tissues at a concentration approx. 2 to 15 times higher than in healthy tissue. Because of the medication's ability to fluoresce, this selective buildup in tumor tissue represents the critical basis for efficient resection of the tumor tissue, in which the tumor is removed as completely as possible but the healthy tissue is not removed.
For diagnosis or for surgery, the tissue to be investigated is irradiated with blue or violet or UV-vicinity light after a suitable delay time following administration of the photosensitizer. The photosensitizer, which is present at an elevated concentration in the tumor tissue because of higher metabolism, is excited by this light and then exhibits a typical red fluorescence and begins to fluoresce under the excitation light. The tumor typically begins to glow red or pink under the illumination, and thereby stands out visually from the healthy tissue (see EP-A1-1 691 229).
In addition to the fluorescence described above, a so-called autofluorescence of the tissue can in some cases also be triggered. This arises from endogenous fluorescent dyes, excitation occurring in most cases by way of fairly short-wavelength blue or UV-vicinity light.
In addition to targeted labeling of tumors and tissues, surgical fluorescence microscopy can also serve to make blood vessels visible, by the fact that a fluorescing substance is once again, as described above, administered to the patient and can be excited and seen through the blood vessel walls. Even the most delicate blood vessels can be located in this fashion; this is helpful especially when blood vessels need to be clamped or in fact not damaged. In this connection, surgical fluorescence microscopy is also particularly advantageous for checking a bypass. This often involves the use of infrared angiography, in which light in the near-infrared (NIR) region is used for excitation and the object field is then observed in a different spectral region.
Other applications make use of (invisible) ultraviolet (UV) light. Other spectral regions between ultraviolet and blue light, and from there to red and the far infrared, are likewise helpfully usable depending on the fluorescence-exciting materials that are used.
Surgical fluorescence microscopes generally comprise an illumination device and a light-guiding unit (illumination beam path) that directs the light of the illumination device into the object field of the microscope and onto that tissue region of the specimen in the object field which is to be diagnosed or treated. The surgical fluorescence microscope further encompasses an image-producing or image-sensing unit (observation beam path) that images the light reflected from the tissue region, or generated there by fluorescence, in an intermediate image plane. Multiple intermediate image planes can also be provided in a surgical microscope, for example for observation with eyepieces or for imaging onto a documentation device, sensor, chip, or the like.
The light-guiding unit is referred to hereinafter as an “illumination beam path,” whereas the image-forming or image-sensing unit, which delivers the light received from the object field to an observer's eye or eyes and prepares it, is referred to as an “observation beam path.”
The light-guiding unit can also encompass, in the illumination beam path, optical waveguides for guiding the light radiated onto the object field to be investigated. This is usual in particular in the case of external illumination devices not integrated into the surgical microscope, and in the case of endoscopes or the like. In surgical microscopes such illumination devices having optical waveguides are frequently used because they allow the hot and relatively heavy light source to be mounted remotely from the microscope body.
The observation beam path encompasses as a rule a binocular tube having eyepieces and/or at least one video camera at a video output.
In the field of surgical fluorescence microscopy, DE 10 2007 034 936 A1, for example, which presents a stereoscopic binocular magnifier (for purposes of the invention, a magnification apparatus for surgery and fluorescence observation), is known from the existing art. The binocular magnifier encompasses two monocular observation beam paths that, because they are arranged in the form of eyeglasses, together form (for purposes of the invention) a binocular stereoscopic observation beam path. Arranged between the two monocular observation beam paths is an illumination device that illuminates the object field, or the specimen being observed, via an illumination beam path or excitation beam path. A first optical filter that is transparent substantially only in the excitation wavelength region is provided in the excitation beam path. Also provided in the observation beam path is at least one further optical filter that is transparent in the fluorescence wavelength region and in addition has only a reduced transparency in the excitation wavelength region, so that the region surrounding the fluorescing area—illuminated by means of excitation light and reflecting that light—is in principle visible.
EP 0 930 843 B1 furthermore discloses an apparatus for photodynamic diagnosis in which the specific configuration of excitation filters in the illumination beam path, and/or of observation filters in the observation beam path, is indicated. FIGS. 2 to 4 therein in particular show conventional combinations of excitation filters and observation filters that, in the respective intersection region of the filter effects of these filters, i.e. in the region in which the transmittance characteristics (transmittance curves) of the filters cross one another, make it evident that at that point light waves from the excitation filter can also pass through the observation filter, but are partly absorbed and are thus available at a low level, or with little brightness, for illumination of the object field. Known filters of this kind could typically be used in the context of the invention as an excitation filter and first observation filter. An alternative filter combination is depicted in FIG. 2a of DE-A1-195 48 913, which is likewise usable in the context of the present invention as a basic construction.
Another configuration from the existing art shows electronically fed-back adjustment of the illumination light via outcoupling of image information from the object field via a computer and an electrically adjustable filter wheel (FIG. 1 of DE-A1-1 102 52 313).
A disadvantage of all known systems is that they exhibit an unmodifiable contrast ratio in the object field, i.e. that the ratio between the reflection of the excitation light from the excitation illumination system at the tissue in the object field, and the visible emission of the fluorescing substances or tissue parts (the fluorescence response), is substantially constant over a wide brightness intensity range of illumination strength from the illumination device. For example, if a blue excitation illumination device is used along with ALA as a photosensitizer, and if the fluorescence response thus occurs in the red spectral region, the tumor labeled, for example, in red is then always visible in its blue-illuminated surroundings in the object field at a constant contrast (relatively consistent ability to distinguish), regardless of the intensity of the excitation light from the illumination device. This contrast ratio is, as a rule, defined on the basis of a standardized surgical environment, so that it represents an optimum for a majority of users and a majority of applications.
In practice, however, there are a large number of external influencing factors that can cause a reduction in this contrast. For example, the ambient lighting in the operating room, the nature of the surrounding tissue, the nature of the tumor cells, the photosensitizer dosage, the nature of the tissue having the buildup, the patient's current metabolism, etc., have an influence on contrast. The subjective perception of various users or surgeons can also be different, for example including their color vision and mood at the time, and their subjective observation requirement. One doctor, for example, might want better orientation within the surgical field, which corresponds to a background illumination (reflected excitation light) that is relatively stronger with respect to the emission intensity and thus to lower contrast as compared with the fluorescing area; another doctor in turn may emphasize optimum detectability of tumor tissue, which corresponds (as the inventor has recognized) to greater contrast between the background illumination and the fluorescing area, and to a greater difference in intensity between emission and reflection.